A comparison of heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major

Background: The goal of this study was to compare heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major.

Method: In this cross-sectional study, 60 patients with beta thalassemia major and 60 patients with beta thalassemia intermedia who had clinically no symptoms of arrhythmia and clinically normal heart function were evaluated using 24-hour ambulatory electrocardiogram monitoring and echocardiography. For data analysis SPSS ver.20 software was used. A P-value of less than 0.05 was considered statistically significant.

Results: The mean age of the beta thalassemia intermedia patients was 24.18 ± 7.9 years and the mean age in beta thalassemia major was 24.38 ± 7.7 years (P>0.05). Premature atrial contractions (PACs) were observed in 14 (23.3%) patients with beta thalassemia intermedia and in 22 (36.6%) beta thalassemia major patients. Premature ventricular contractions (PVCs) were detected in 8 (13.3%) patients in the beta thalassemia intermediate group and 16 (26.6) patients in the beta thalassemia major group, respectively. The left ventricular diastolic dimension, end-diastolic volume, and stroke volume were significantly higher in beta thalassemia intermedia group (P<0.05). Pulmonary acceleration time as an indicator of pulmonary pressure was lower in beta thalassemia intermedia group.

Conclusion: Both atrial and ventricular arrhythmias were more common in the beta thalassemia major group. Higher end-diastolic volume and stroke volume were detected in the beta thalassemia intermedia group. Pulmonary acceleration time was lower in the beta thalassemia intermedia group, which can be an indicator of higher pulmonary pressure.     

Hb Wilde and Hb Patagonia: two novel elongated beta‐globin variants causing dominant beta‐thalassemia

We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant β‐thalassemia‐like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB:c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a ‘GT’ dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated β‐globin chains with modified C‐terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated β‐globins would affect the formation of the αβ dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.     

Echocardiographic findings in a patient with primary pulmonary hypertension

This is a report of the echocardiographic findings in a 9-year-old white female with primary pulmonary arterial hypertension confirmed by catheterization and later at autopsy. The reported findings of an absent “a” wave, a flat diastolic E to F slope, and a midsystolic closure of the pulmonic valve were observed. In addition, tricuspid valve prolapse was noted. Prolapse of the tricuspid valve may be part of the mechanism of tricuspid insufficiency in a patient with pulmonary hypertension.     

Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness

Heart disease is the leading cause of mortality and morbidity in β‐thalassemia major (β‐TM). Aggregability of abnormal red cells and membrane‐derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young β‐TM patients compared with 40 age‐ and sex‐matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b⁺) and ErMPs (glycophorin A⁺) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 μg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non‐compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D‐dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.     

Effect of combination therapy of hydroxyurea with l‐carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with β‐thalassemia intermedia

Background: l‐Carnitine and magnesium have antioxidant properties. They have the potential to stimulate production of fetal hemoglobin and stabilize the RBC membrane, respectively. Several studies have also shown the beneficial effects of hydroxyurea in thalassemic patients. We assessed the effect of combination therapy of hydroxyurea with l ‐carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with β‐thalassemia intermedia. Methods: One‐hundred‐and‐twenty patients with thalassemia intermedia (range, 4–35 yr; mean, 19 ± 6.4 yr) who had no need for blood transfusion or requirement for blood transfusion with an interval of >6 months were randomly selected. All patients had been on hydroxyurea for >6 months. They were randomly divided into four groups: group A (hydroxyurea alone); group B (hydroxyurea and l ‐carnitine); group C (hydroxyurea and magnesium chloride); and group D (hydroxyurea, l ‐carnitine and magnesium chloride). Results: In groups B, C, and D, mean Hb and hematocrit increased during 6‐month treatment (P < 0.001). Echocardiographic studies revealed a significant decrease in left ventricular end‐diastolic diameter in group B (P = 0.032), increase in pulmonary acceleration time in group C (P = 0.012), and increase in left ventricular ejection fraction in groups C and D (P < 0.000 and 0.006, respectively). Conclusion: Combination of hydroxyurea with l ‐carnitine or magnesium could be more effective in improving hematologic parameters and cardiac status in patients with β‐thalassemia intermedia than hydroxyurea alone.     

Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state

The pathogenesis of pulmonary hypertension (PAH), a serious complication in thalassemia, is not well understood. Thromboembolism has been postulated as one of the causative factors; however, there are currently limited specific data on its role. To examine whether increased platelet activation and hypercoagulability are linked to PAH, 25 beta-thalassemia major and beta-thalassemia intermedia patients were evaluated with Doppler echocardiograms for estimation of pulmonary artery pressure and with laboratory assays for indications of a prothrombotic state. The association of clinical variables and abnormal coagulation assays with PAH was determined. PAH was identified in 17 (68%) patients; mean pulmonary artery systolic pressure was 39.8 +/- 5.4 mm Hg. PAH was significantly associated with prior splenectomy, older age, and evidence for chronic hemolysis, diagnosed in both transfused (n = 10) and nontransfused (n = 7) patients. Increased platelet activation, measured by P-selectin, was significantly associated with PAH (P = 0.001). Increased thrombin-antithrombin III level was more prevalent in the presence of PAH, but increased fibrinolysis or low protein C levels were not. This study underscores the role of platelet activation in the development of PAH and stresses its occurrence even among patients who are regularly transfused, especially those who are older and have had splenectomies.     

Heart rate variability in beta‐thalassemia patients

Background: Cardiac failure remains the major cause of death in beta‐thalassemia major (TM). Reduced heart rate variability (HRV) is associated with a higher risk of arrhythmias after myocardial infarction and heart failure. We evaluated HRV in TM patients and its relationship with hemodynamics and echocardiographic parameters during a 6‐month follow‐up. Methods: Thirty‐four TM patients (19 ± 10 yr) and 20 healthy subjects (17 ± 6 yr) were evaluated. Hematologic, biochemical, echocardiographic and HRV parameters were determined at entry and at 6‐month follow‐up. Time and frequency domain HRV parameters were analyzed from 24‐h recorded electrocardiograms. All TM patients received blood transfusion and chelation therapy. Results: Both time and frequency domain HRV parameters were markedly reduced in TM patients, compared to the control. The significantly improved HRV was seen in correlation with higher hemoglobin (Hb) level when compared within TM group at different time point. No correlation was seen between HRV and serum ferritin, reactive oxygen species (ROS) and non‐transferrin bound iron (NTBI). Conclusion: HRV is depressed in TM patients. HRV was significantly correlated with Hb level, suggesting that anemia greatly influences the cardiac autonomic balance.     

Cardio‐selective and non‐selective beta‐blockers in chronic obstructive pulmonary disease: effects on bronchodilator response and exercise

Background: Patients with chronic obstructive pulmonary disease (COPD) often have co‐existing cardiovascular disease and may require beta‐blocker treatment. There are limited data on the effects of beta‐blockers on the response to inhaled β₂‐agonists and exercise capacity in patients with COPD. Objective: To determine the effects of different doses of cardio‐selective and non‐selective beta‐blockers on the acute bronchodilator response to beta‐agonists in COPD, and to assess their effects on exercise capacity. Methods: A double‐blind, randomized, three‐way cross‐over (metoprolol 95 mg, propranolol 80 mg, placebo) study with a final open‐label high‐dose arm (metoprolol 190 mg). After 1 week of each treatment, the bronchodilator response to salbutamol was measured after first inducing bronchoconstriction using methacholine. Exercise capacity was assessed using the incremental shuttle walk test. Results: Eleven patients with moderate COPD were recruited. Treatments were well‐tolerated although two did not participate in the high‐dose metoprolol phase. The area under the salbutamol–response curve was lower after propranolol compared with placebo (P = 0.0006). The area under the curve also tended to be lower after high‐dose metoprolol (P = 0.076). The per cent recovery of the methacholine‐induced fall was also lower after high‐dose metoprolol (P = 0.0018). Low‐dose metoprolol did not alter the bronchodilator response. Oxygen saturation at peak exercise was lower with all beta‐blocker treatments (P = 0.046). Conclusion: Non‐selective beta‐blockers and high doses of cardio‐selective beta‐blockers may inhibit the bronchodilator response to β₂‐agonists in patients with COPD. Beta‐blockers were also associated with lower oxygen saturation during exercise. The clinical significance of these adverse effects is uncertain in view of the benefits of beta‐blocker treatment for cardiovascular disease.     

Pulmonary hypertension and beta-thalassemia major: report of a case, its treatment, and a review of the literature

Pulmonary hypertension is a common complication of beta-thalassemia major. We report a case of successful treatment of pulmonary hypertension in a patient with beta-thalassemia major and review the literature on pulmonary hypertension and beta-thalassemia major. A 28-year-old man with beta-thalassemia major, splenectomy, hepatitis C, and hemosiderosis who presented with increasing dyspnea on exertion was diagnosed with pulmonary hypertension. After receiving continuous epoprostenol infusion and desferoxamine, his functional capacity and hemodynamic status improved. To our knowledge, this is the first case of pulmonary hypertension associated with beta-thalassemia treated with continuous epoprostenol infusion and desferoxamine. Epoprostenol, beneficial in the treatment of other types of pulmonary hypertension, may ameliorate the morbidity and mortality of pulmonary hypertension associated with thalassemia.     

Primary pulmonary hypertension: M-mode and two-dimensional echocardiographic findings

In two young men subsequently found to have primary pulmonary hypertension, echocardiographic findings suggested an atrial septal defect. Additionally, contrast echocardiography demonstrated right-to-left shunting at the atrial level. Cardiac catheterization demonstrated severe pulmonary hypertension with patent foramen ovale. Thus, primary pulmonary hypertension may result in findings similar to atrial septal defect on echocardiography, particularly if a foramen ovale is present.